339.1 🎓 醫孞生版

339.1.0.1 📌 䞀頁重點

339.1.0.1.1 Nephrotic Syndrome
339.1.0.1.1.1 Definition (Classic Pentad)
  1. Proteinuria > 3.5 g/24 h (or UPCR > 3.5 or UACR > 2200 mg/g)
  2. Hypoalbuminemia (< 3.5 g/dL, often < 2.5)
  3. Edema (peripheral, periorbital, anasarca; pleural effusion, ascites)
  4. Hyperlipidemia (↑ LDL, TG)
  5. ± Hypercoagulability (loss of antithrombin III; ↑ thrombosis especially renal vein)
339.1.0.1.1.2 Pathophysiology
  • Glomerular basement membrane / podocyte injury
  • Increased permeability to protein
  • Albumin loss → low oncotic pressure → edema + compensatory hepatic lipoprotein synthesis
  • Loss of immunoglobulins → ↑ infection risk
  • Loss of vitamin D-binding protein → vitamin D deficiency
  • Loss of thyroxine-binding globulin → hypothyroidism (sometimes)
339.1.0.1.1.3 Common Causes

Primary (Idiopathic) — More Common in Adults: - Minimal Change Disease (MCD): most common in children (80%); ~ 10-20% adults - Focal Segmental Glomerulosclerosis (FSGS): most common cause of NS in adults in US - Membranous Nephropathy (MN): most common in older adults; anti-PLA2R, anti-THSD7A, anti-NELL-1 - Membranoproliferative GN (MPGN) / C3 glomerulopathy (C3G): complement-mediated - IgA Nephropathy (some can have nephrotic features)

Secondary: - Diabetic Kidney Disease (DKD) — most common cause of NS globally - Amyloidosis (AL, AA, hereditary) - Light chain deposition disease (MM-related) - Hepatitis B (MN) - Hepatitis C (MPGN, mixed cryoglobulinemia) - HIV (HIVAN — FSGS variant) - Drugs: NSAIDs, lithium, gold, penicillamine, ICI - Cancer: MN (paraneoplastic), AL - Pregnancy: preeclampsia, lupus - Sjögren, RA, sarcoidosis

339.1.0.1.1.4 Complications
  • Thromboembolism (renal vein, DVT, PE)
  • Infections (encapsulated organisms — S. pneumoniae)
  • Edema (severe, anasarca)
  • Hyperlipidemia + atherosclerosis
  • Acute kidney injury (intravascular volume depletion, drug toxicity, RVT)
  • Vitamin D deficiency
  • Hypothyroidism (rare)
  • Iron deficiency
339.1.0.1.2 Nephritic Syndrome
339.1.0.1.2.1 Definition
  1. Hematuria (dysmorphic RBC + RBC casts)
  2. Hypertension
  3. Edema (mild-moderate)
  4. AKI variable (rising Cr, oliguria possible)
  5. Proteinuria variable (sub-nephrotic typically; can be nephrotic in some)
  6. ± Constitutional symptoms (fever, malaise, joint pain)
339.1.0.1.2.2 Pathophysiology
  • Glomerular inflammation (proliferative)
  • Endothelial damage
  • ↓ GFR (acutely)
  • Hematuria from disrupted GBM
  • Activated complement (often)
339.1.0.1.2.3 Common Causes

Primary: - IgA Nephropathy — most common globally - Post-Infectious GN (PSGN) — strep, staph, others; classic in pediatric - MPGN / C3G — primary or secondary

Secondary (Common): - Lupus nephritis (Class I-VI; ISN/RPS 2003) - ANCA-associated vasculitis (GPA, MPA, EGPA) - Anti-GBM disease (Goodpasture) - Cryoglobulinemic vasculitis (often hep C-associated) - IgA vasculitis (Henoch-Schönlein purpura) - Post-infectious (other than strep — hep B, hep C, HIV, endocarditis) - MPGN (lupus, hep C, monoclonal gammopathy)

339.1.0.1.2.4 Rapidly Progressive GN (RPGN)
  • Subset of nephritic with rapid decline
  • Cr doubles in days-weeks
  • Histology: crescents on biopsy
  • 3 types (Couser classification):
    1. Anti-GBM (Type I) — Goodpasture
    2. Immune Complex (Type II) — lupus, post-infectious, IgA
    3. Pauci-Immune (Type III) — ANCA-associated
  • Emergency: high-dose steroids + cyclophosphamide ± plasmapheresis
339.1.0.1.3 Diagnostic Workup
339.1.0.1.3.1 Initial Tests
  • Urinalysis with microscopy
  • UACR or UPCR (spot)
  • 24-hour urine protein quantification
  • Serum chemistry: Cr, BUN, electrolytes, glucose, albumin
  • Lipid profile: nephrotic-range cholesterol + TG
  • CBC + differential
  • LFTs
339.1.0.1.3.2 Immunology Panel
  • ANA, dsDNA: lupus
  • Complement C3, C4: low in lupus, post-infectious GN, MPGN, C3G, cryoglobulin
  • ANCA: GPA, MPA, EGPA
  • Anti-GBM: Goodpasture
  • Anti-PLA2R: primary MN (70-80%)
  • Anti-THSD7A, anti-NELL-1: less common MN antibodies
  • Anti-streptolysin O (ASO), anti-DNase B: PSGN
  • RF, anti-CCP: RA
  • Cryoglobulins: hepatitis C, lupus
  • Hep B surface antigen, hep C antibody: hepatitis
  • HIV: HIVAN
  • Free light chains + SPEP/UPEP: myeloma, amyloid
  • Complement C5b-9 (MAC), factor B: complement-mediated
339.1.0.1.3.3 Infectious Workup
  • Blood cultures: endocarditis-associated
  • Throat / skin cultures: PSGN
  • Tuberculosis: secondary causes
339.1.0.1.3.4 Imaging
  • Renal ultrasound: size, hydronephrosis, masses, cortical thinning
  • CT: malignancy, vascular
  • Doppler: renal vein thrombosis suspicion
339.1.0.1.3.5 Renal Biopsy (Gold Standard)
  • For definitive diagnosis
  • Light microscopy + immunofluorescence + electron microscopy
  • Indications:
    • Unexplained AKI
    • Nephritic syndrome
    • Nephrotic syndrome in adults (often)
    • Rapidly progressive disease
    • Steroid-resistant
  • Complications: bleeding (1-2%), AV fistula
339.1.0.1.4 General Treatment Principles
339.1.0.1.4.1 Specific Therapy (Ch339)
  • Tailored to specific GN
  • Immunosuppression: steroids, cyclophosphamide, rituximab, MMF, CNIs, IS
339.1.0.1.4.2 Supportive Care
  • ACE/ARB: reduce proteinuria + BP
  • Dietary salt restriction
  • Diuretics: loop ± thiazide; carefully (volume depletion + AKI)
  • Statins: dyslipidemia, CV risk
  • Anticoagulation: prophylactic for high-risk nephrotic (especially MN with severe hypoalbuminemia or large protein loss); LMWH or DOAC
339.1.0.1.4.3 Vaccinations
  • Pneumococcal (PCV20 + PPSV23 — encapsulated risk)
  • Influenza annual
  • COVID-19
  • RSV ≥ 60
  • Hepatitis B
339.1.0.1.4.4 Avoid Nephrotoxins
  • NSAIDs
  • Aminoglycosides
  • Contrast (if possible)
  • Lithium

339.1.0.2 🩺 床邊速查

  • Nephrotic: > 3.5 g/24h protein + hypoalbuminemia + edema + hyperlipidemia ± thrombosis
  • Nephritic: hematuria + RBC casts + HTN + AKI variable
  • Top nephrotic causes: MCD (kids), FSGS, MN (adults), DKD, amyloid
  • Top nephritic causes: IgA, PSGN, lupus, ANCA, anti-GBM, MPGN/C3G
  • RPGN 3 types: anti-GBM, immune complex, pauci-immune (ANCA)
  • Workup: UA + UACR + immunology + biopsy
  • Anti-PLA2R: primary MN (70-80%)
  • C3 low: PSGN, lupus, MPGN, C3G, cryoglobulin